cystic fibrosis- The role of pancreatic enzymew replacement therapy and stool elastase

1. CYSTIC FIBROSIS-CREON & STOOL
ELASTASE
Dr.Vinod.P

2. Pancreatic insufficiency
• Most common gastrointestinal complication of
cystic fibrosis.
• Approximately 85 percent of patients at some
time in their lives.
• Fat malabsorption (Major consequence)

3. PANCREATIC SUFFICIENT
10-15%
PANCREATIC INSUFFICIENT
85-90%
CYSTIC FIBROSIS
PANCREATIC SUFFICIENT
Pancreatic function correlates strongly with
genotype in patients with CF

5. Pancreatic function tests
.
DIRECT PFT INDIRECT PFT
Lundth
Secretin
CCK
Stool elastase
Fecal fat
Serum trypsinogen
Fecal chymotrypsin
Pancreolauryl test
Breath tests

6. INDIRECT PANCREATIC FUNCTION
TESTS
• Simpler and easier to perform.
• Main role in diagnosis of advanced PEI since
they are much less sensitive than direct tests for
diagnosis of earlier stages of PEI.

7. • Serum trypsinogen- not sensitive for advanced
disease
• Fecal fat- steatorrhea implies a loss of greater
than 90 percent of normal enzyme secretory
output.
• Collection & processing is cumbersome

8. Fecal chymotrypsin and elastase-1
• Enzymatic products of pancreatic secretion that
remain relatively stable during transport
through the gastrointestinal tract.

9. Fecal chymotrypsin
• Using the secretin-CCK test as reference
standard, sensitivity is 85 % for advanced PEI,
but only 49% for mild and moderate PEI
• Affected during intestinal transport and may be
diluted in the presence of concomitant
diarrhea.
• Patients must stop exogenous enzymes for two
days prior to the collection.

10. Fecal elastase -1
• Pancreatic elastase-1 appears to be more stable
than chymotrypsin during intestinal transit.
• Exogenous enzymes do not interfere with the
elastase test assay as they do with the
chymotrypsin assay

11. • Using direct PFT as reference standard, fecal
elastase-1 has approximately 100 % sensitivity for
severe, 77 to 100 % for moderate, and 0 to 63
percent sensitivity for mild PEI .
• Specificity is approximately 93 percent .
• These studies suggest higher sensitivity and
specificity of fecal elastase compared with fecal
chymotrypsin.

12. Pancreatic elastase
• In addition to extending a protolytic activity, it
combines with bile acids and neutral steroids in
the intestinal lumen to transport cholesterol and
its metabolites along the intestinal tract.
• Possible because of the extraordinary stability of
this enzyme during its passage.

13. • Elastase concentration in stool is five times
higher than pancreatic juice, hence fecal elastase
concentration accurately reflects the amount of
enzyme secreted from the pancreas.

14. Age-All ages Range(Ugm elastase/gm stool)
NORMAL >200
MODERATE TO SLIGHT
ISUFFICIENCY
100-200
SEVERE
INSUFFICIENCY
<100

15. • In view of low sensitivity and sensitivity in early
disease results of fecal elastase testing should be
combined with clinical scenario.

16. PERT( Pancreatic enzyme replacement therapy)
• Multiple formulations of pancreatic enzymes
exist with different combinations of lipase,
protease, and amylase.

17. Different formulations
• PANCREAZE
• CREON
• ZENPEP
• ULTRESA
• VIOKACE
• PERTYE

18. CREON
LIPASE AMYLASE PROTEASE
Creon 3 3000 15000 9500
Creon 6 6000 30000 19000
Creon 12 12000 60000 38000
Creon 24 24000 120000 76000
Creon 36 36000 180000 11400

19. DOSING
• Weight based- <4yrs- 1000lipase units/kg/meal
>4yrs- 500lipase units/kg/meal
Dose can be increased up to 2500units/kg/meal
depending upon response.

20. • Fat based- For infants with known amount of
formula or NG feedings.
• 2000lipase units/120ml of formula or DBF
• Maximum lipase units per day not more than
10000/kg.

21. • Patients who fail to respond to maximal doses of
PERT- ranitidine or omeprazole.
• Higher pH for the entire product to be released.
• But limited evidence along with adverse effects.

22. Adequacy of PERT
• Elastase not useful as a measure to monitor the
effectiveness of PERT because it is a measure of
pancreatic function and not a measure of
malabsorption.
• Can check fecal fat

23. Adverse effects of PERT
• Prolonged contact of the enzyme supplements
with oral mucosa may cause ulcers, especially
with the powdered form.
• To prevent this complication, children should
learn to swallow capsules as early as possible.

24. Administration in younger children
• Open the capsules and microspheres should be
administered with food (eg, applesauce), even in
infants.
• The mouth should be inspected after eating and
rinsed with water, milk, or formula if necessary
to remove any beads clinging to the oral mucosa

25. • Fibrosing colonopathy- Limited evidence with
no established causal relation
• Maximum dose of 2500 lipase units/kg body
weight per meal (or less than 10,000
lipase units/kg body weight per day) is
recommended .

26. Ref
• Uptodate

27. THANK YOU